The prostaglandins exibit a wide range of physiological activities and have been finding widespread medicinal applications because of their diverse and useful biological actions such as peripheral circulatory improvement, vasodilation, antiulceration, hypotensive, induction of labor, thrombolytic, and antiasthmatic. In recent years, these compounds have been studied for possible new indications such as anticancer, osteometabolism improvement, antiviral, hepatic protection, diuresis In particular, the naturally occurring prostacyclin is a local hormone predominantly produced in vivo from the vascular wall of arteries; owing to its potent physiological effects such as platelet agglutination inhibitory activity and vasodilating activity, this local hormone is an important factor which regulates in vivo cellular functions, and hence an attempt has been made to use the naturally occurring prostacyclin per se as a pharmaceutical product [P. J. Lewis, J. O. Grady et al., Clinical prostacyclin, Raven Press, N.Y. (1981)].
On the other hand, however, when these useful prostaglandins are applied as pharmaceutical products, various problems are encountered with respect to the in vivo instability inherent in the prostaglandins, side effects attributable to a wide range of their physiological effects, and the difficulties of formulations due to their chemical instability.
Thus, intensive studies have been carried out at home and abroad with regard to chemically stable synthetic prostacyclin derivatives comparable to naturally occurring prostacyclin in terms of biological actions.
Meanwhile, attempts have been made to stabilize chemically unstable prostacyclin in dosage form as well as to improve its drug efficacy. For example, propositions have been put forth regarding a method of stabilizing the prostacyclin as the clathrate compound using cyclodextrin (Joseph Scesitri et al., Japan Laid-Open Patent Showa 54-56685), a method of stabilizing the prostacyclin with surface active agents (Moo Yang Chou et al., Japan Laid-Open Patent Showa 55-15470), a pharmaceutical preparation by first obtaining a new ester derivative of prostacyclin with the higher fat solubility, emulsifying this ester derivative in a fat, and maintaining its activity comparable to that of the parent prostacyclin (Fukaya et al., Japan Laid-Open Patent Showa 60-13779), and so forth.
The fat emulsions containing PGE.sub.1 or PGA.sub.1 have recently been proposed as the stabilized prostaglandin fat preparations which possess vasodilating, platelet agglutination inhibitory, and hypotensive activities [Mizushima et al., Japan Laid-Open Patent Showa 58-222014 and Japan Laid-Open Patent Showa 59-141518; and Mizushima et al., Ann. Rheum. Diseases, 41, 263 (1982); Pharm. Pharmacol., 35, 398 (1983)]. Such techniques are applied to the preparation of the anti-tumor agents; a proposal has been set forth with respect to the improvement of selective delivery of anticancer drugs to the target organ (Okamoto et al., Japan Laid-Open Patent Showa 59-122423).